title: Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy.
abstract: A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4(+) T-cell count was 753 cells/mm(3), and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviral-treated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.
authors.affiliation: San Francisco General Hospital, Building 80, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110, USA. hhatano@php.ucsf.edu
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.forename: Eric L
authors.initials: EL
authors.lastname: Delwart
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Joan
authors.initials: J
authors.lastname: Dunn-Williams
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Linnen
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral